BI23 Skin checks out: pembrolizumab-associated pemphigoid nodularis

Abstract

Immune checkpoint inhibitors (CPIs) are increasingly recognized to provoke immune-related cutaneous adverse events. Clinical appearances may be atypical, but diagnostic accuracy is important as the implications for treatment and continuation, suspension or cessation of CPIs may be significant. We present a case of pembrolizumab-associated pemphigoid nodularis in which immunopathological studies were key to diagnosis and informing subsequent management. A 56-year-old woman undergoing neoadjuvant treatment for breast cancer with pembrolizumab–­paclitaxel–carboplatin–doxorubicin–cyclophosphamide developed an intensely pruritic rash on her limbs and trunk. Examination revealed widespread excoriated papules and nodules, some with superficial erosions. She had no frank blisters but evidence of oral mucositis. The clinical differential diagnoses included lichen planus and nodular prurigo secondary to CPI-associated pruritus. Histopathology demonstrated a markedly acanthotic epidermis with hyperkeratosis, hypergranulosis, occasional colloid bodies, mild spongiosis, focal subepidermal fibrin deposition and a perivascular lymphocytic infiltrate with occasional eosinophils. Direct immunofluorescence (DIF) showed strong linear IgG and C3 deposition along the basement membrane zone, supporting a diagnosis of pemphigoid nodularis (PN). Indirect immunofluorescence (IIF) studies were negative. The rash and oral mucositis improved with prednisolone and topical steroids, and planned adjuvant pembrolizumab was suspended. PN is a rare variant of bullous pemphigoid (BP). Clinically, it may closely resemble nodular prurigo, but it has immunological features of BP with positive DIF, IIF or both. To our knowledge, there are only two previously reported cases of PN, and its immunopathogenesis is uncertain. The diagnosis of PN in this case was revealed by DIF findings. Accurate diagnosis is critical to management as PN usually requires systemic treatment and consideration of CPI cessation, whereas nodular prurigo treatment focuses on controlling the itch–scratch cycle and inflammation, and continuation of CPI therapy. This case highlights the critical importance of immunopathology studies in diagnosis and optimal management of CPI-associated dermatoses.